Ophthalmic U.V. absorptive emollient

ABSTRACT

Method of using ophthalmic dosage of aqueous aloe vera gel as emollient and absorbent of UV radiation to shield eye retina by topically applying said gel in the eye.

BACKGROUND OF THE INVENTION

Although ultra-violet radiation has long been recognized as a factor inthe development of cutaneous cancer, aging of the skin, and mutagenicchanges, it is only within the last decade or less that ultra-violetradiation has been universally recognized as a causative factor inocular pathogenesis.

In humans, the eye has evolved into a sophisticated organ havingneurophysiologic responses to photons in a certain portion of theelectromagnetic spectrum, that provides a constant detailed map of theimmediate environment. The action spectrum for these responses lieprimarily within the 400-700 NM wavelength range, which has been labeledthe visible spectrum or "Light".

The maximum of the eye's spectral response corresponds roughly to themaximum of solar spectral irradiance. Because solar UV radiation ispresent during most of the daylight hours, the eye may be exposed dailyto some amount of solar ultraviolet radiation throughout life.

Wavelengths shorter than approximately 290NM or UV-C are partially orcompletely absorbed within the cornea and conjunctiva. The acute effectsof exposure to these wavelengths are primarily those of conjunctivitisand a corneal inflammation reaction known as photokeratitis. Theinflammatory reaction of the outermost layer of the eye to UV-C and UV-Bradiation can be similar to that of the skin in some respects.

The clinical progress or picture of photokeratitis follows acharacteristic course. For example, after exposure, there is a period oflatency which varies somewhat inversely with the amount of exposure. Thelatent period may be as short as 30 minutes or as long as 24 hours butit is typically 6 to 12 hours.

Conjunctivitis, which is often accompained by an erythema of the skinsurrounding the eyelids, is associated with the sensation of a foreignbody or "sand" in the eyes, varying degrees of photophobia (intoleranceto light), lacrimation (tearing), and blepharospasm (spasm of lidmuscles). Corneal pain can be very severe, and the individual is usuallyincapacitated for some period of time. These acute symptoms usually lastfrom 6 to 24 hours and almost all discomfort disappears within 48 hours.Very rarely does conjunctivitus causing exposure result in permanentdamage.

However, unlike the skin, the ocular system does not develop toleranceto repeated ultraviolet exposure. Swelling or shrinking of groups ofcorneal epithelial cells leads to visibly recongizable stippling orirregular mosaic granulation of the corneal surface. With UV dosesgreater than the threshold for photokeratitis, surface epithelial cellsshow nuclear fragmentation, mid-epithelial cells show vacuole formation,and basel cells show inhibition of mitosis and clouding of the cornealstroma occurs. Inflammation is also present in the conjunctiva wherevasodilation, edema, and inflammatory cell infiltrate is followed bydesquamation.

When the cornea is damaged or replaced by surgery, the eye in generalbecomes very sensitive and the retina becomes vulnerable to ultra violetradiation below about 325 nm or in the UV-B and UV-C ranges. This is theopposite of what happens with a healthy or non-relaced cornea. In thehealthy or undamaged eye, absorption of radiation by the cornea and lensof the human eye is such that very little radiation of wavelengthsshorter than 390 NM reaches the retina.

The retina (tunica interna) is a delicate nervous membrane, upon whichthe images of external objects are received. Its outer surface is incontact with the choroid; its inner with the vitreous body. Behind, itis continuous with the optic nerve; it gradually diminishes in thicknessfrom behind forward and extends nearly as far as the ciliary body, whereit ends in a jagged margin, the ora serrata. Here the nervous tissues ofthe retina end, but a thin prolongation of the membrane extends forwardover the back of the ciliary processes and iris, forming the parsciliatis retinae and pars inidica retinae. This forward prolongationconsists of the pigmentary layer of the retina together with a stratumof columnar epithelium. The retina is soft, semitransparent, and of apurple tint in the fresh state, owing to the presence of a coloringmaterial named rhodopsin or visual purple; however, it soon becomesclouded, opaque, and bleached when exposed to sunlight. Prolongedexposure of the retina to UV-B and UV-C wavelengths causes damage to theretina.

SUMMARY OF THE INVENTION

Accordingly, it is a principal object of the present invention toprovide a method for soothing the eye and protecting the retina of theeye from UV-B and UV-C radiations by delivering an ophthalmicchromophore dosage of an emollient gel into the eye, whereby prolongedretention of said chromophore is provided.

It is a further object of the invention to provide a method for soothingthe mucous membranes of the eye and protecting the retina of the eyefrom UV-B and UV-C radiations after corneal transplants by delivering anophthalmic chromophore dosage of an emollient gel into the eye, wherebyprolonged retention of said chromophore is provided.

It is a yet further object of the invention to provide a method forsoothing the mucous membranes of the eye and protecting the retina ofthe eye from UV-B and UV-C radiation by using a single gel as both anemollient and UV absorber or chromophore, as the sole dosage means toachieve prolonged retention of said emollient chromophore in the eye.

Another object further still is to provide a method for soothing the eyeand protecting the retina of the eye from UV-B and UV-C radiation byusing an aloe vera gel dispersion as both an emollient and UV absorberor chromophore as the sole dosage means to achieve prolonged retentionof said emollient chromophore in the eye.

A still further object of the invention is to utilized ultra violetlight plus aloe vera as a regimen for treatment of corneal ulcers.

These and other objects of the invention will become more apparent fromthe descriptions hereafter set further.

DETAILED DESCRIPTION OF THE INVENTION

U.S. Pat. No. 3,470,109 discloses a method of making reconstitutablealoe vera gel in dry crystalline form for use in the manufacture ofpharmaceutical preparations; however, there has been no determination ofthe potential of the gel for use as liquid sunglasses applied topicallyin the eyes.

The cornea portion of the eye is considered to be a fat-water-fatsandwich. Chemical analysis shows the lipid content of the epitheliumand endothelium to be 100 times greater than that of the corneal stroma.As a result, the epithelium and endothelium are relatively impermeableto electrolytes but are readily penetrated by fat-soluble substances.

The present invention discovery is that the differential solubility ofpenetration of the cornea is such that aloe vera gel is absorbed by thecornea fatty layer, and aloe vera gel can be used as an emollientophthalmic chromophore dosage in the eye as an absorbent to prevent UV-Band UV-C radiation from reaching the retina.

While not wishing to be bound by a theory as to why or how said gelfunctions in this manner, it is worthy to note that the Merck Indexindicates that the principal active ingredient of aloe is aloin whichhas the structure: ##STR1## It is believed that when the aloe vera gelcontaining this active ingredient is topically placed in the eye, a UV-Band UV-C absorption spectrum equilibrium is established between the tearfilm and epithelium of the cornea of mammals.

Prolongation of the equilibrium appears to be accomplished by theviscous gel dispersion and/or a slow erosion of the viscous surface. Thechromophore containing viscous or gel composition of aloe vera have aprolonged retention time in the eye and remain in contact with thesurface of the eye for periods of from about 2 to about 4 hours.

The aloe vera gel can be used alone, or in admixture with a highmolecular weight polymer which forms viscous gels. In this connection,polymers which can be used in the present invention have a molecularweight of from about 1 million to about 6 million, and are characterizedby carboxylic or anhydride functional groups and preferably containsfrom 2 to 7 carbon atoms per functional group. The gels which formduring the preparation of the aloe vera gel polymer dispersion have aviscosity of from about 40,000 to about 300,000 cps at 20 rmp (spindle7) at 25° C. generated by an RVT Brookfield Viscometer, and preferablyfrom about 75,000 to about 200,000 cps, most preferably from about90,000 to about 150,000 cps.

Suitable polymers useful in the present invention arecarboxypolymethylene, a carboxy vinyl polymer, (available under thetrade name Carbopol from the B. F. Goodrich Company); and ethylenemaleic anjydride, (available under the trade name EMA from the MonsantoCompany).

When the aloe vera gel is used alone, a purified solution containingfrom 1% to 8% of the gel will suffice to provide liquid sunglasses whichare absorbed by the cornea fatty layer to set up the UV-B and UV-Cequilibrium between the tear film and the epithelium of the cornea.

In admixture with the high molecular weight polymers, the total weightof gel and polymer should still come up to between 4 to 6% by weight ofthe composition.

EXAMPLE I

The outer skin from leaves of the aloe vera plant are stripped-off toobtain the gel from the interior of the leaves. The gel is placed in ablender and mercerized from 3 to 5 minutes, and then filtered through a60 mesh stainless steel screen. Purified water is then stirred into thegel to bring the gel contant to 4% by weight.

Thereafter, ophthalmic dosages of about 50 μL of the 4% gel areadministered directly into the eyes of an albino rabbit, and the gel isactive as a UV-B and UV-C absorber in the rabbit's eyes for a period of2 to 4 hours.

EXAMPLE II

Aloe vera gel in the form of anydrous crystals is reconstituted byadding deionized water to restore the physical and chemical propertiesof the gel before it was lyophilized. When sufficient water has beenadded to make the gel about 6% by weight of the dispersion, the gelcompositions contain about 94% by weight of water trapped in the matrixand is clear so that the vision is not blurred, because the gelrefractive index is similar to that of tears.

Ophthalmic dosages of about 50 μl of the 6% gel are administereddirectly into the eyes of an albino rabbit and the gel is active as aUV-B and UV-C absorber in the rabbit's eyes for a period of 2 to 4hours.

EXAMPLE III

A 3.8% by weight of ethylene maleic anhydride (available under the tradename of EMA -91 from Monsanto) solution in purified water is preparedand mixed using a high speed mixer with a 2% by weight dispersion ofaloe vera gel in purified water.

Ophthalmic dosages of about 50 μl are administered directly into theeyes of an albino rabbit and the gel is active as a UV-B and UV-Cabsorber in the rabbit's eyes for a period of 2 to 4 hours.

Topically applied aloe vera chromophore gel emollient compositions ofthe invention, when placed in the eyes via drops, provide a film of UV-Band UV-C absorption spectrum equilbrium between the tear film and theepithelium of the cornea, and in addition to absorbing UV light whichregular sun-glasses would absorb, the gel additionally absorbs theestimated 30 to 35% of UV-B and UV-C radiation that normally reaches theeyes from points above, below and from the sides of regular sun glasses.

In the context of the invention aloe vera gel alone, or together withthe high molecular weight polymer can be used in the crystalline formand later reconstituted with purified water, prior to use as chromophoredrops.

A method of preparing the crystalline form of aloe vera is disclosed inU.S. Pat. No. 3,470,109.

When utilizing aloe vera gel in crystalling form, deionized or distilledwater is added in the aloe vera gel in crystalling form, to obtainreconstituted aloe vera gel having the same physical properties andchemical properties of the aloe vera gel before it was lyophilized. Bythe amount of water added, the viscosity and other features of the aloevera gel may be controlled. In general, a viscosity in the range ofabout 40,000 to about 300,000 cps will suffice, more preferably fromabout 75,000 to about 200,000 cps, and most preferably from about 90,000to about 150,000 cps.

The germicidal properties of ultra violet light are well known andwidely used for sterilization, and in view of the resistence of manyviruses, fungi and bacteria to antibiotics, the invention utilizes acombination of ultra violet light treatment and aloe vera to treatcorneal ulcers

Peak germicidal activity occurs at a wavelength of about 265 nm (mosteffective wavelength against viruses and fungi as well as againstbacteria), and nucleoprotein absorption of UV light has a similar peak.In view of this fact, it is believed that the germicidal effect is aresult of nucleo protein destruction.

For reasons not fully clear some actinic keratitis is produced mosteffectively at a wavelength of 288 nm.

However the invention discovery is that superimposition of thegermicidal and keratitis producing spectral curves indicate that, atabout 253.7 nm the germicidal effect is 85% of maximum, whereas thekeratitis effect is only 20% of maximum.

Utilizing this fact, a low pressure mercury vapor lamp calibrated atabout 253.7 nm is used to expose the eyes of an albino rabbit held inthe open position to radiation for 30 seconds. During this time, thelamp is held approximately 5 mm away from the cornea.

The exposed cornea is then treated by delivering an ophthalmicchromophore emollient gel of aloe vera to the surface of the eye toestablish a UV absorption spectrum equilibrium between the tear filmepithelium of the cornea. This post treatment is an important stepbecause UV radiation effects are accumulative, and the cornea must beprotected for a period of from about 5 to about 10 days from atmosphericand environmental UV in the UV-C and UV-B ranges. After about 5 to 7days after the post treatment step, the epithelium of the cornea isnormally replaced by normal growth processes.

The length of time the rabbit's eye is exposed to radiation will dependupon the kin and types of viruses, fungi and bacteria present, however,it has been found that an exposure period of from about 30 to 300seconds will suffice in the context of the invention. While thepreferred wavelength is 253.7 nm, it has been found that wavelengths±50nm from this value is operable in the invention context.

What is claimed is:
 1. An ophthalmic aqueous gel for preventing UV-B andUV-C radiation from reaching the eye retina upon placement in the eye toestablish a UV absorption spectrum equilibrium between the tear film andepithelium of the cornea of the eye, said gel comprising an aloe verachromophore emollient gel present in amounts of from about 1% to about8% by weight in said ophthalmic aqueous gel.
 2. An ophthalmic aqueousgel for preventing UV-B and UV-C radiation from reaching the eye retinaupon placement in the eye to establish a UV absorption spectrumequilibrium between the tear film and epithelium of the cornea of theeye, said gel comprising an aloe vera chromophore emollient gel and agel-forming ethylene maleic anhydride polymer having a molecular weightin excess of 1,000,000, wherein the combined weights of chromophore andpolymer are from 4 to 6 percent by weight of said ophthalmic aqueousgel; said ophthalmic gel having a viscosity of from about 40,000 toabout 300,000 cps.
 3. An aqueous gel in accordance with claim 2 whereinsaid polymer has a molecular weight from about 1,000,000 to about6,000,000.
 4. An aqueous gel in accordance with claim 2 wherein said gelhas a viscosity of from about 75,000 to about 200,000 cps.
 5. An aqueousgel in accordance with claim 2 wherein said gel has a viscosity of fromabout 90,000 to about 150,000 cps.
 6. A method for delivering anophthalmic chromophore gel to the surface of the eye to prevent UV-B andUV-C radiation from reaching the eye retina by establishing a UVadsorption spectrum equilibrium between the tear film and epithelium ofthe cornea over extended periods of time, comprising adding to purifiedwater aloe vera gel in an amount of 4 to 6% by weight of said opthalmicgel and introducing said ophthalmic gel into the eye.
 7. The method ofclaim 6 wherein said gel further includes a gel-forming high molecularweight ethylene maleic anhydride polymer having a molecular weight inexcess of 1,000,000 and said gel has a viscosity of between about 40,000and about 300,000 cps.
 8. A method in accordance with claim 7 whereinsaid polymer has a molecular weight of from about 1,000,000 to about6,000,000.
 9. A method in accordance with claim 7 wherein said aqueousgel has a viscosity of from about 75,000 to about 200,000 cps.
 10. Amethod in accordance with claim 7 wherein said gel has a viscosity offrom about 90,000 to about 150,000 cps.
 11. A method of treating cornealulcers comprising exposing the eye of a subject of to U.V. radiation inthe range of from about 203.7 to about 303.7 nm for a period of fromabout 30 to 300 seconds, anddelivering an ophthalmic chromophoreemollient gel to surface of the eye to establish a U.V. absorptionspectrum equilibrium between the tear film and epithelium of the cornea;said gel is selected from the group consisting of aloe vera aloe or inadmixture with a gel-forming ethylene maleic anhydride polymer having amolecular weight in excess of 1,000,000.